Since bisantrene was shown to be up to 5x more effective than doxorubicin and epirubicin in MCF-7 cell lines resistant to other therapies, I decided to do some further digging. As I have expressed, I am very confident that FTO expression was measured before and after use of bisantrene, and the results of this are to be presented soon. What you may not know and what I think is extremely important to know going into the POC breast cancer trial is the breast cancer types known to overexpress these MCF-7 cells. I think that taking a kill two birds with one stone philosophy would be advantageous because this could be an opportunity to showcase phase II trial results without necessarily focusing specifically on FTO.
My immediate reasoning for thinking so are:
- bisantrene shown to be up to 5x effective in breast cancer cell lines MCF-7 resistant to chemotherapy treatments doxorubicin and epirubicin
- MCF-7 breast cancer cells included into the study as they are known to overexpress FTO (1,2)
- breast cancer POC trial is happening regardless of FTO opportunity and the addition of biomarker or indicator measurement may be cost effective
Firstly, multiple studies support that MCF-7 breast cancer cell lines are found in ER/PR+ and HER2- breast cancers (3) (see below).
A study reports that
69% of breast cancers are ER/PR+ and HER2-, with the greater majority of ER+ breast cancers occuring in postmenopausal women (4; see below). I have spoken previously of the relationship between increased obesity, estrogen production and resulting increased FTO expression (5). This represents a very large addressable market that is likely to have MCF-7 breast cancer cells. Please, keep in mind that FTO overexpression has been linked with HER2 and tripple negative (6), but for the purpose of this write up, I have focused specifically on MCF-7 cells in ER/PR + and HER2- breast cancer. The MCF-7 breast cancer cell lines have been linked with proliferation (7), which has also been linked to FTO overexpression in breast cancer (6). Based on the information made available in the rediscovery of bisantrene review, I can make no connection to breast cancer subtype and bisantrene efficacy.
To my best available knowledge, I do not know of any method available that can accurately measure breast cancer FTO expression without taking a biopsy, so I doubt that will happen in the breast cancer POC trial. However, based on this information I have presented, I find it highly reasonable to assume that breast cancer patients will be screened for ER/PR + and HER2- breast cancer types and assumptions could be made about the main cell type and FTO expression in this breast cancer type. I think that it would be an advantegous opportunity to get phase II clinical data that may start to show the relationship between bisantrene, FTO inhibition, and breast cancer outcomes in real patients.
I also speculate whether the George Clinical Trial Review has had to modify the POC breast cancer trial on the basis of the data obtained from the preclinical breast cancer trial and wonder if we will see FTO results before receiving the George Clinical POC Breast Cancer Trial Review.
All IMO - DYOR
1.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437932/2.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452952/3.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665029/4.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960520/pdf/BMRI2014-836769.pdf5.
https://hotcopper.com.au/threads/pillar-1-fto-new-thread.5839654/page-302?post_id=515195476.
https://ar.iiarjournals.org/content/35/6/3147.full7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751723/pdf/ott-13-12845.pdf
(20min delay)